Description
Udenafil is the fourth in a class of drugs targeting the inhibition of the enzyme
phosphodiesterase 5 (PDE5) for the treatment of erectile dysfunction. Inhibition of
PDE5 results in the increase in endogenous cyclic guanosine monophosphate
(cGMP) concentrations in the penile corpus cavernosum. cGMP induces smooth
muscle cell relaxation and subsequent increased blood flow leading to a sustainable
erection. Udenafil is a potent antagonist of human PDE5 with an IC
50 of 8.25nM
and a comparable selectivity profile as sildenafil for the other PDEs. Unlike tadalafil,
it does not inhibit PDE11, which has been implicated in myalgia and
testicular toxicity. Furthermore, udenafil produced up to a 91% vaginal
penetration success rate and up to a 67% intercourse completion rate compared to a
29% completion rate by placebo. Overall patient satisfaction, measured by a
standard global assessment question, was 86% compared to only 26% in the placebo
group. The most frequently recorded adverse events were mild-to-moderate
facial flushing and headache.
Description
Udenafil is an inhibitor of phosphodiesterase 5 (PDE5).
In vivo, udenafil (1 and 5 mg/kg) increases lung cGMP levels, attenuates the development of compensatory right ventricular hypertrophy, and reduces pulmonary arterial wall thickening in a rat model of monocrotaline-induced pulmonary hypertension. It increases creatine clearance and decreases blood urea nitrogen (BUN) and serum malondialdehyde (MDA) levels in a rat model of renal ischemia-reperfusion injury. Udenafil (0.3 and 10 mg/kg) induces penile erections in conscious rabbits and in rabbits with acute spinal cord injury.
Chemical Properties
Off-White Solid
Originator
Dong-A (South Korea)
Uses
Udenafil is an oral phosphodiesterase 5 inhibitor used for the treatment of erectile dysfunction.
Definition
ChEBI: Udenafil is a sulfonamide.
Synthesis
Udenafil has a unique pharmacokinetic
profile with a relatively rapid onset and sufficiently long
duration (Tmax 1-1.5 hr, t1/2 11-13 hr) to make it effective
for up to 24 hours. Synthesis of this racemic compound
started with commercially available 2-propoxybenzoic
acid (160). The free acid 160 was converted to
it acyl chloride with thinoy chloride in refluxing dichloromethane,
which was condensed with 4-amino-1-methyl-3-
propyl-1H-pyrazole-5-carboxamide (161) with TEA and
DMAP in dichloromethane to yield carboxamide 162 in 85%
yield from 160. Compound 162 was sulfonated with chlorosulfonic
acid to yield benzenesulfonyl chloride 163 in 67%
yield, which was treated with racemic 2-(1-methylpyrrolidin-
2-yl)ethylamine (164) in dichloromethane to afford sulfonamide
165 in 80% yield. Finally, compound 165 was cyclized
with tBuOK in refluxing tBuOH to give udenafil (XXII) in
81% yield.
References
[1] K K KANG. DA-8159, a new PDE5 inhibitor, attenuates the development of compensatory right ventricular hypertrophy in a rat model of pulmonary hypertension.[J]. Journal of International Medical Research, 2003, 31 6: 517-528. DOI:
10.1177/147323000303100608[2] YUSUF ZLüLERDEN. The renoprotective effects of mannitol and udenafil in renal ischemia-reperfusion injury model.[J]. Investigative and Clinical Urology, 2017, 58 4: 289-295. DOI:
10.4111/icu.2017.58.4.289[3] KYUNG KOO KANG. DA-8159, a new PDE5 Inhibitor, Induces Penile Erection in Conscious and Acute Spinal Cord Injured Rabbits[J]. European urology, 2003, 43 6: Pages 689-695. DOI:
10.1016/s0302-2838(03)00153-2
